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Development of a method for quantitative determination and preliminary pharmacokinetics study of a new anticancer agent
* 1, 2 , 1, 2 , 1, 2 , 1, 2 , 3 , 3 , 2 , 1, 2
1  Vorozhtsov Novosibirsk Institute of Organic Chemistry, 630090, Russia, Novosibirsk, Lavrentjev prosp., 9
2  Novosibirsk State University, 630090, Russia, Novosibirsk, Pirogova, 1
3  Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Russia, Novosibirsk, Lavrentjev Prosp, 10

Abstract:

For the treatment of cancer, inhibitors of the reparation systems are needed. One of the specific targets is the enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1). Inhibition of this enzyme can increase the sensitivity of tumor cells to drugs used to treat cancer. Earlier, the substance KS-389 was obtained, which in in vitro experiments showed a synergistic effect against glioblastoma cells when was administrated together with temozolomide. In this work we developed a HPLC-MS/MS method for the quantittion of the agent KS-389 in mice whole blood. A calibration curve was obtained in a concentration range of 2-2000 ng/ml. Using the developed method, a preliminary pharmacokinetics study of the substance was carried out.

When administered intraperitoneally at a dose of 5 mg/kg, a dosage form based on tween-80 provided better bioavailability compared to oral administration. The maximum concentration of KS-389 of about 450 ng/ml was observed 1.5-2 hours after administration. The full clearance of the agent was 6 hours after the administration showing normal pattern of the pharmacokinetics.

Keywords: cancer, glioblastoma, LC-MS/MS, pharmacokinetics
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